Treatment of Rickets in Autosomal-Recessive Hypophosphatemic Rickets Type 2 (ARHR2) with Biallelic ENPP1 Mutations and No Arterial or Cardiac Calcification

Autosomal-recessive hypophosphatemic rickets type 2 (ARHR2) is a rare inherited cause of rickets driven by biallelic loss-of-function mutations in the ENPP1 gene. Managing these patients is challenging, and the presence or absence of vascular or cardiac calcification critically shapes which treatments are appropriate.

Clinical Scenario This protocol applies to patients with confirmed ARHR2 — biallelic ENPP1 mutations — who present with hypophosphatemic rickets in the absence of arterial or cardiac calcification. ENPP1 deficiency may be associated with arterial, cardiac, and/or articular calcification or may present as generalised arterial calcification in infancy; the presence of such calcifications precludes treatment with active vitamin D. In patients without calcification, a treatment approach using oral phosphate supplementation together with active vitamin D is applicable.

Treatment Approach (Partial Overview) The reported regimen in this rare condition involves a combination of oral phosphate salt supplementation and calcitriol (active vitamin D). Specific dosing targets and the full structured algorithm are available in the complete protocol. Dosages, frequency, monitoring intervals, and the complete clinical algorithm are detailed in the full protocol — see link below.

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References

DOI: 10.1007/s00467-022-05505-5

Treatment of patients with ARHR2 is challenging due to its rarity and the fact that ENPP1 deficiency not only causes hypophosphatemic rickets but may also be associated with arterial, cardiac and/or articular calcification or may present as generalized arterial calcification in infancy.

The presence of calcifications precludes treatment with active vitamin D.

In a small series including 6 ARHR2 patients, the reported dosages of phosphate salts (based on elemental phosphate) and calcitriol amounted to 40 mg/kg day and 15 ng/kg per day, respectively.

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